Influence Of Human Papillomavirus Research Articles

The Role of Human Papilloma Virus in the Pathogenesis of Sinonasal Inverted Papilloma; A Metanalytical Study

Abstract Background Sinonasal inverted papilloma (SNIP) is a benign and relatively rare tumor of the nasal cavity and paranasal sinuses, most commonly originates from the lateral nasal wall or maxillary sinus from the schneiderian sinonasal epithelium. There is a male predominance with a male-to-female ratio of 3.4:1. Sinonasal Squamous Cell Carcinoma (SCC) associated with IP has an incidence of approx. 0.38 cases/million persons/year. Patients with carcinoma in IP are older than those IP patients without carcinoma. Some authors assume an influence of Human Papilloma Virus (HPV) subtyping. Transcripts of HPV DNA were found in malignant IP. Objective To perform a meta-analytical study to determine the relationship between human papilloma virus and the occurrence of sinonasal inverted papilloma. Patients and Methods The review will be restricted to RCTs, clinical trials, and comparative studies, either prospective or retrospective, which studied the outcome of Negative HPV group versus Positive HPV group of patients. Data Sources Medline databases (PubMed, Medscape, ScienceDirect. EMF-Portal) and all materials available in the Internet till 2021. Data Extraction If the studies did not fulfill the inclusion criteria, they were excluded. Study quality assessment included whether ethical approval was gained, eligibility criteria specified, appropriate controls, and adequate information and defined assessment measures. Results In our study HPV positive cases were (23.6%) (107/ 452) among SNIP patients. Malignant SNIP rate was (10.8%) (49/ 452). HPV positive cases among malignant SNIP patients was (51.02%) (25/49). Conclusion In this meta-analytical study HPV positive cases were (23.6%) (107/ 452) among SNIP patients. Malignant SNIP rate was (10.8%) (49/ 452). Though the etiology of SNIP remains controversial, the studies reviewed in this study indicate a role for HPV infection. Further studies in the future regarding the impact of other risk factors on the occurrence of SNIP would be of value, these factors include angiogenic factors, environmental factors, genetic, viral and chronic sinonasal inflammation.

Identification of the HNSC88 Molecular Signature for Predicting Subtypes of Head and Neck Cancer.

Head and neck squamous cell carcinoma (HNSC) exhibits genetic heterogeneity in etiologies, tumor sites, and biological processes, which significantly impact therapeutic strategies and prognosis. While the influence of human papillomavirus on clinical outcomes is established, the molecular subtypes determining additional treatment options for HNSC remain unclear and inconsistent. This study aims to identify distinct HNSC molecular subtypes to enhance diagnosis and prognosis accuracy. In this study, we collected three HNSC microarrays (n = 306) from the Gene Expression Omnibus (GEO), and HNSC RNA-Seq data (n = 566) from The Cancer Genome Atlas (TCGA) to identify differentially expressed genes (DEGs) and validate our results. Two scoring methods, representative score (RS) and perturbative score (PS), were developed for DEGs to summarize their possible activation functions and influence in tumorigenesis. Based on the RS and PS scoring, we selected candidate genes to cluster TCGA samples for the identification of molecular subtypes in HNSC. We have identified 289 up-regulated DEGs and selected 88 genes (called HNSC88) using the RS and PS scoring methods. Based on HNSC88 and TCGA samples, we determined three HNSC subtypes, including one HPV-associated subtype, and two HPV-negative subtypes. One of the HPV-negative subtypes showed a relationship to smoking behavior, while the other exhibited high expression in tumor immune response. The Kaplan-Meier method was used to compare overall survival among the three subtypes. The HPV-associated subtype showed a better prognosis compared to the other two HPV-negative subtypes (log rank, p = 0.0092 and 0.0001; hazard ratio, 1.36 and 1.39). Additionally, within the HPV-negative group, the smoking-related subgroup exhibited worse prognosis compared to the subgroup with high expression in immune response (log rank, p = 0.039; hazard ratio, 1.53). The HNSC88 not only enables the identification of HPV-associated subtypes, but also proposes two potential HPV-negative subtypes with distinct prognoses and molecular signatures. This study provides valuable strategies for summarizing the roles and influences of genes in tumorigenesis for identifying molecular signatures and subtypes of HNSC.

Exploring the potential impact of human papillomavirus on infertility and assisted reproductive technology outcomes

Human papillomavirus (HPV) is a common sexually transmitted disease that has been linked to both cancer and reproductive health issues. While its impact on fertility and pregnancy success has been studied, there is still too little evidence about the influence of HPV on assisted reproductive technology (ART). Therefore, there exists a need for HPV testing in couples undergoing infertility treatments. Infertile men have been found to have a higher prevalence of seminal HPV infection, which can compromise sperm quality and reproductive function. As such, it could be important to investigate the correlation between HPV and ART outcomes in order to improve the quality of evidence. Understanding the potentially detrimental effects of HPV on ART outcomes may have promising important implications for the management of infertility. This minireview summarizes the so far limited developments in this area and highlights the major need for further well-designed studies to address this issue.

Impact du statut HPV sur l’évolution nutritionnelle au cours de la chimioradiothérapie des patients atteints d’un cancer de l’oropharynx

PurposePatients with oropharyngeal cancer are at high nutritional risk before and during treatment. Little is known about the influence of human papillomavirus (HPV) infection on nutritional status and its evolution during treatment. Materials and methodsA single-center retrospective study was conducted between August 2017 and December 2020 including 48 patients (14 HPV-induced: HPV+ and 34 non-HPV-induced: HPV−) with oropharyngeal squamous cell carcinoma treated by radiotherapy±chemotherapy (RT/CT). Nutritional risk at the time of tumor assessment (TA) was assessed by weight loss, swallowing ability, and the presence of digestive disorders in 4 stages of increasing severity. Nutritional status was assessed by weight and nutrition risk index (NRI) at the time of TA, before the start and at 3 months from the end of RT±CT. During RT±CT, the NRI and the systemic inflammatory response index (SIRI=neutrophils * monocytes/lymphocytes) were assessed weekly. ResultsHPV+patients were at lower nutritional risk at TA (50% grade ≥2 vs 85%, P=0.02), lost more weight (6% of their body weight vs 3%, P=0.05), and increased their SIRI by 7.5 points more than HPV− patients (P=0.04) during RT/CT. ConclusionHPV+ oropharyngeal cancer patients are at high nutritional risk even in the absence of undernutrition at the outset of management.

Influence of Human Papillomavirus on Alveolar Bone and Orthodontic Treatment: Systematic Review and Case Report.

Background: As the human papillomavirus (HPV) infections are detected in healthy oral mucosa as well as in oral lesions, dental practitioners have an important role in detecting any possible lesions that might be caused by this virus. Therefore, the aim of this study was to investigate the outcomes of orthodontic treatments and HPV infections and to report a rare case of ongoing orthodontic treatment superposed on an HPV infection. Methods: An electronic English literature research of the articles published between the years 2011–2021 was conducted between December 2021–February 2022, accessing PubMed, Web of Science, Embase, Scopus, and Google Scholar. The terms “HPV”, “orthodontics”, “orthodontic treatment”, “tooth movement”, “tooth mobility”, and “malocclusion” were searched. The following inclusion criteria were pursued: articles published in English language; studies reporting HPV infection in subjects with past or ongoing orthodontic treatment; and case reports of subjects with HPV and orthodontic treatment. Exclusion criteria were: articles in languages other than English, studies related to malignancies other than HPV and orthodontic treatment; and studies reporting patients with HPV and no orthodontic treatment. Results: Following the systematic review, which includes six papers, a case of orthodontic treatment superposed on a HPV infection is presented. Conclusion: Incumbent, postponed HPV infection on an ongoing orthodontic treatment might affect treatment outcome and patient compliance.

Decreased CD1a + and CD83 + cells in tonsillar squamous cell carcinoma regardless of HPV status.

Dendritic cells (DCs) are specialized antigen-presenting cells that play a critical role in the immune response against human papillomavirus (HPV) infection, and represent a therapeutic target in cancer.Objective:To identify and quantify DCs in tonsillar squamous cell carcinoma (TSCC) under the influence of HPV infection.Methodology:CD1a and CD83 antibodies were used to identify immature dendritic cells and mature dendritic cells by immunohistochemistry in 33 primary TSCC and 10 normal tonsils (NTs), respectively. For the TSCC samples, the number of DCs per area was evaluated in the intra- and peritumoral compartments. For the NTs, the quantification of DCs was evaluated in the intra- and peritonsillar compartments. HPV detection methods were determined according to the ASCO Clinical Practice Guidelines from the College of American Pathologists Guideline (2018).Results:There were fewer intratumoral CD1a+ DCs in the HPV-positive and HPV-negative TSCC groups than in the NT group (p<0.05). In the peritumoral compartment, there were fewer CD83+ DCs in the HPV-positive and HPV-negative TSCC groups than in the NT group (p<0.001). The quantification of DCs subtypes showed no statistical differences between HPV-positive and HPV-negative TSCC groups (p>0.137). Patients with HPV-positive TSCC had significantly better overall survival rate than those with HPV-negative TSCC (p=0.004).Conclusion:Tumor activity contributes to DC depletion regardless of intralesional HPV positivity. An improved prognosis has been reported in patients with HPV-positive TSCC.

Diseases associated with human papillomavirus: from understanding of etiopathogenesis to prevention and rational management tactics

The purpose: to consider modern concepts of epidemiology, biological characteristics, pathogenesis, clinical manifestations, principles of therapy and prevention of human papillomavirus infection.Basic provisions. In the last decade, there has been a steady increase in diseases associated with the human papillomavirus (HPV). The prevalence of human papillomavirus infection of the genitals in the world has increased more than 10 times, it is found in 13 % of the population. Cervical cancer remains one of the most common forms of HPV-associated malignancy in women. About 570 thousand new cases of cervical cancer are diagnosed in the world every year, while the increase in incidence over the past 10 years was 7.8 %, and mortality was 13.1 %. In recent years, scientists have paid close attention to the study of assessing the effect of HPV on the endometrium and the degree of its participation in the development of GGE. From the standpoint of the latest scientific data, the generality of the influence of HPV on any epithelium should be considered through the prism of squamous cell metaplasia. Currently, there are still many unsolved scientific and practical issues, primarily related to the regional characteristics of the prevalence of various types of HPV, which determines the direction of cervical screening, as well as clinical manifestations during coinfection, dictating the need for a differentiated approach to patient management tactics.Conclusion. A review of modern literature data indicates that most studies on various aspects of the influence of HPV on the reproductive health of women remain the subject of discussion, which dictates the need for further research.

Influence of human Papilloma Virus (hPV) infection on early pregnancy.

HPV infection in early pregnancy may be a cause of miscarriage. Pregnancy significantly increases the risk of HPV infection. While ascending intrauterine infection with colonization of the trophoblast is commonly observed, descend- ing hematogenous infection should also be considered. The aim of the study is to assess the prevalence of HPV infection and its influence on pregnancy. The study was conducted in the years 2010-2015 on a group of 143 pregnant women. The study group consisted of 84 women with abnormal course of the first trimester of pregnancy. The control group consisted of 59 women with normal pregnancy who delivered healthy neonates. Samples of cervix tissue along with samples of tropho- blast or placenta were taken for the study. The presence and genotype of the HPV virus were detected using a BIOTOOL B&M Labs set. Statistical analysis was conducted using R software. The rate of HPV infection in the entire studied population was 13% (19/143): the virus was confirmed in 18% (15/84) of patients in the study group and in 7% (4/59) of the control group. HR HPV was detected in 13 patients in the study group and three patients in the control group. HR HPV infection was more frequent in patients with an abnormal course of the first trimester of pregnancy (p = 0.03). HR HPV trophoblast infection was found only in patients in the study group (p = 0.02). In two members of the study group, the HPV virus was found in the trophoblast only. The obtained results may confirm the presence of adverse effects of HPV infection on early pregnancy. HR HPV trophoblast infection was observed only in women with 1st trimester complications. The presence of HPV only in trophoblast samples in some patients may suggest a descending - hematogenous route of primary infection.

HPV infection and bacterial microbiota in breast milk and infant oral mucosa.

ObjectiveWe investigated the association between bacterial microbiota in breast milk and the infant mouth. The influence of human papilloma virus (HPV) infection on infant oral microbiota was also assessed.Material and methodsAltogether 35 breast milk and 35 infant oral samples with known HPV status were selected from the Finnish Family HPV Study cohort. In total, there were 31 mother-infant pairs. The microbiota composition was characterized by 16S rRNA gene sequencing (V3-V4 region).ResultsHPV DNA was present in 8.6% (3/35) of the breast milk and 40% (14/35) of the infant oral samples. Eight shared genera between breast milk and infant oral were found; these included Streptococcus, Staphylococcus, Unclassified Gemellaceae, Rothia, Veillonella, Haemophilus, Propionibacterium and Corynebacterium. HPV status was not associated with either microbiota richness or diversity in the infant mouth. However, the infant oral microbiota clustered in different groups according to HPV status. We detected higher abundance of Veillonella dispar (p = 0.048) at species level in HPV negative infant oral samples. We did not detect differences in the breast milk microbiota composition related to HPV infection due to only three HPV positive milk samples.ConclusionsHPV infection is associated with distinct oral bacterial microbiota composition in infants. The direction of causality underlying the phenomenon remains unclear.

Evidence of synergistic relationships between HIV and Human Papillomavirus (HPV): systematic reviews and meta-analyses of longitudinal studies of HPV acquisition and clearance by HIV status, and of HIV acquisition by HPV status.

IntroductionObservational studies suggest HIV and human papillomavirus (HPV) infections may have multiple interactions. We reviewed the strength of the evidence for the influence of HIV on HPV acquisition and clearance, and the influence of HPV on HIV acquisition.MethodsWe performed meta‐analytic systematic reviews of longitudinal studies of HPV incidence and clearance rate by HIV status (review 1) and of HIV incidence by HPV status (review 2). We pooled relative risk (RR) estimates across studies using random‐effect models. I 2 statistics and subgroup analyses were used to quantify heterogeneity across estimates and explore the influence of participant and study characteristics including study quality. Publication bias was examined quantitatively with funnel plots and subgroup analysis, as well as qualitatively.Results and DiscussionIn review 1, 37 publications (25 independent studies) were included in the meta‐analysis. HPV incidence (pooled RR = 1.55, 95% CI: 1.29 to 1.88; heterosexual males: pooled RR = 1.95, 95% CI: 1.62, 2.34; females: pooled RR = 1.63, 95% CI: 1.26 to 2.11; men who have sex with men: pooled RR = 1.36, 95% CI: 1.01 to 1.82) and high‐risk HPV incidence (pooled RR = 2.20, 95% CI: 1.90 to 2.54) was approximately doubled among people living with HIV (PLHIV) whereas HPV clearance rate (pooled RR = 0.53, 95% CI: 0.42 to 0.67) was approximately halved. In review 2, 14 publications (11 independent studies) were included in the meta‐analysis. HIV incidence was almost doubled (pooled RR = 1.91, 95% CI 1.38 to 2.65) in the presence of prevalent HPV infection. There was more evidence of publication bias in review 2, and somewhat greater risk of confounding in studies included in review 1. There was some evidence that adjustment for key confounders strengthened the associations for review 2. Misclassification bias by HIV/HPV exposure status could also have biased estimates toward the null.ConclusionsThese results provide evidence for synergistic HIV and HPV interactions of clinical and public health relevance. HPV vaccination may directly benefit PLHIV, and help control both HPV and HIV at the population level in high prevalence settings. Our estimates of association are useful for mathematical modelling. Although observational studies can never perfectly control for residual confounding, the evidence presented here lends further support for the presence of biological interactions between HIV and HPV that have a strong plausibility.

Epidemiology of Hypopharyngeal and Oropharyngeal Cancers in Japan

BACKGROUND: Both hypopharyngeal cancer and oropharyngeal cancer are rare malignancies. However, it is reported that the incidences of these cancers have increased in Japan. It is known that smoking and drinking are risk factors for both cancers. Recently, human papillomavirus (HPV) is regarded as a risk factor for oropharyngeal cancer. In this article the changes in the mortality rates of these cancers are described from the viewpoint of descriptive epidemiology. METHODS: The numbers of deaths due to the 2 cancers from 1979 to 2016 were obtained from the vital statistics of Japan. The numbers of persons in each of the years were obtained from the census and vital statistics of Japan. RESULTS: For males, the ratio of the numbers of deaths from hypopharyngeal cancer/oropharyngeal cancer has been almost constant, at about 2. The crude mortality rate of hypopharyngeal cancer for males has been increasing. The rate in 2016 was about 9 times that in 1979. The male/female ratio has been increasing as well, which is due to the large increase for males and the small increase for females. The crude mortality rate of oropharyngeal cancer for males has been increasing. The rate in 2016 was more than 10 times that in 1979. In the group 50-59 years of age, the crude mortality rate of hypopharyngeal cancer for males has been almost constant. However, in the groups aged 70 years and older, it has been rapidly increasing. The changes in the crude mortality rates of oropharyngeal cancer were similar to those of hypopharyngeal cancer. In the group aged 50-59 years, the crude mortality rate remained stable. However, in the groups 70 years of age and older, it has been rapidly increasing. The age-adjusted mortality rate of hypopharyngeal cancer for males has been increasing, and there has been no clear sign of a decrease. The age-adjusted mortality rate of oropharyngeal cancer for males has been increasing as well, and there has been no sign of a decrease. While the smoking rate has been decreasing since 1966, the number of cigarettes per smoker per day was increasing during the period from 1960 to 2000. The percentage of heavy drinkers among the population remained almost stable. CONCLUSIONS: For males, since the age-adjusted mortality rates of the 2 cancers have been increasing, it is certain that their incidences have been increasing. Their incidences may largely increase in older age groups. The contribution of the number of cigarettes per smoker to the pathogenesis of these 2 cancers may be larger than that of the smoking rate. The influence of HPV on oropharyngeal cancer was not apparent in the data for mortality rates.

Influence of human papillomavirus on the clinical presentation of oropharyngeal carcinoma in the United States.

Much of what is known about the significance of human papillomavirus (HPV) in oropharyngeal squamous cell carcinoma is derived from single-institution retrospective studies, post hoc analyses of tissue specimens from clinical trials, and tissue bank studies with a small sample size. The objective of this study is to investigate the impact of HPV on the frequency and clinical presentation of oropharyngeal carcinoma in a large, national sample with information from patients who underwent HPV testing. Retrospective, cross-sectional study. We identified a comprehensive national sample of 8,359 patients with oropharyngeal carcinoma and known HPV status diagnosed between 2010 and 2011 within the National Cancer Database. Multivariable logistic regression was used to assess correlates of patient and tumor characteristics on HPV status. Among patients with oropharyngeal carcinoma, the frequency of HPV-related squamous cell carcinoma in the United States was 65.4%. HPV-related oropharyngeal carcinoma was associated with younger age, male sex, and white race (P < 0.001). Advanced primary tumor stage was associated with HPV-negative disease (P < 0.001), whereas increasing nodal burden was associated with HPV-positive disease (P < 0.001). Despite less-advanced nodal disease, HPV-negative tumors were associated with a higher likelihood of metastasis at presentation (P < 0.001). HPV now accounts for the majority of newly diagnosed oropharyngeal carcinoma in the United States and is associated with a distinct clinical profile, supporting efforts to re-evaluate the staging and treatment paradigm for HPV-associated oropharyngeal cancer. 4. Laryngoscope, 127:2270-2278, 2017.

The influence of human papilloma virus (HPV) infection on early pregnancy – pilot study

The influence of human papilloma virus (HPV) infection on early pregnancy – pilot study

Prognostic significance of HPV status in postoperative squamous-cell carcinoma of the head and neck.

There are limited data on the prognostic significance of human papillomavirus (HPV) status in relation to traditional risk factors for head and neck squamous-cell carcinoma (HNSCC) in the postoperative setting. To clarify the impact of HPV status on the risk for HNSCC in the postoperative setting. We retrospectively evaluated an institutional cohort of 128 patients with HNSCC patients who had been treated with definitive surgery with or without adjuvant radiotherapy or chemoradiotherapy. Patient, disease, and treatment factors were analyzed as potential prognostic indicators. Lymph node extracapsular extension (ECE), perineural invasion (PNI), and lymphovascular space invasion (LVSI) positivity predicted poorer locoregional control (LRC), disease-free survival (DFS), and overall survival (OS). Positive margins related to poorer DFS and OS. HPV status alone did not predict LRC, DFS, or OS. Compared with patients who were HPV-positive and ECE-negative, both HPV-positive and HPV-negative patients with ECE experienced significantly poorer OS (78.6%, 60%, and 43.7%, respectively; 𝑃 = .010 and 𝑃 = .018, respectively). Retrospective, single-institution study; small patient cohort; short follow-up time. The influence of HPV in postoperative HNSCC seems limited compared with traditional risk factors such as ECE, LVSI, and PNI. De-escalation of postoperative treatment based on HPV status alone should be approached with caution.

The effect of human papillomavirus 16 E6 gene silenced by small interfering RNA on the expression and the promoter hypermethylation status of E-cadherin in cervical cancer SiHa cell line

Objective To investigate the influence of human papillomavirus (HPV) 16 E6 gene silencing by small interfering RNA (siRNA) on the expression and the promoter hypermethylation status of E-cadherin (E-cad) in cervical cancer SiHa cell line. Methods siRNA which used lentivirus as the vector was used to knock down the HPV16E6 gene in cervical cancer SiHa cell line. The expression levels of HPV16E6 mRNA, E-cad mRNA and protein in siRNA-HPV16E6 SiHa cell line were detected by RT-qPCR and Western blot, respectively. Methylation specific PCR (MSP) method was used to detect the methylation status of E-cad gene (CDH1) promoter in siRNA-HPV16E6 SiHa cell line. Results The E-cad mRNA expression levels in siRNA E6 group, empty vector group and blank control group were 4.755±1.085, 1.224±0.840, 1.327±1.221, respectively. The protein expression levels were 0.616± 0.019, 0.325±0.016, 0.299±0.015, respectively. The expressions of E-cad mRNA and protein in siRNA E6 group were significantly higher than those in the empty vector group and blank control group (F= 21.346, P 0.05). After knocking down HPV16E6 gene, the methylation status of E-cad gene was weakly positive, and the intensity of the amplified products was significantly weaker than that in the empty vector group and blank control group, while the unmethylation amplification was positive. Conclusions Knocking down the HPV16E6 gene increases the expression of E-cad in cervical cancer SiHa cell line, and decreases the level of CDH1 promoter methylation. To a certain extent, it partly reverses the hypermethylation status of CDH1 promoter, and causes E-cad to be re-expressed. Key words: Cadherins glycoprotein; Human papillomavirus 16E6; Methylation; Small interfering RNA; Cervical neoplasms; SiHa cell line

Human Papillomavirus Vaccine-Induced Cytokine Messenger RNA Expression in Vaccinated Women.

The objective of this work was to evaluate the influence of human papillomavirus (HPV) vaccination on peripheral blood mononuclear cell (PBMC) proliferation and cytokine gene transcription. PBMCs isolated after HPV immunization were incubated with HPV vaccine, phytohemagglutinin, or buffer. Cell proliferation was assessed by MTT reduction assay. RNA was extracted from PBMCs, and the relative concentration of cytokine messenger RNA (mRNA) transcripts (IFN-β, IFN-γ, IL-12, TNF-α, IL-6, IL-17, or IL-10) relative to transcription of the β-actin gene was determined by real-time polymerase chain reaction. PBMC proliferation in response to HPV vaccine and PHA were greater than that observed in unstimulated cells (p<0.001). Cytokine mRNAs were upregulated in stimulated PBMC cultures. The median increase in vaccine-stimulated cultures was: IFN-β=334.4-fold; IL-12=46.33-fold; IFN-γ=12.64-fold; IL-6=9.07-fold; IL-17=7.33-fold; IL-10=6.47-fold; and TNF-α=2.36-fold. The IFN-β expression was significantly higher (p<0.05). Proliferative PBMC responses and multiple cytokine gene expression were detected in women who received the HPV vaccine.

Influence of human papillomavirus and p16INK4a on treatment outcome of patients with anal cancer

BackgroundThe purpose of this study was to evaluate HPV-DNA and p16INK4a (p16) expression as prognostic markers for outcome in patients with anal cancer. MethodsFrom January 2000 to December 2011 a cohort of 105 anal cancer patients was treated with definitive chemoradiation at our institution. Tumor biopsies from 90 patients were analyzed for HPV-DNA by polymerase chain reaction and for p16 expression by immunohistochemistry. ResultsMedian follow-up was 48.6months (range 2.8–169.1months). HPV-DNA or p16-expression was found in 75 anal cancers each (83.3%), concordance was detectable in 70 tumors (77.8%). Significantly improved overall survival (OS) [77.1% vs. 51.4%, p=0.005], progression-free survival (PFS) [64.0% vs. 35.0%, p<0.001] and improved local control [81.0% vs. 55.9%, p=0.023] was found for concomitant HPV- and p16-positive anal carcinomas (cHPPAC) in univariate analysis. Multivariate analysis showed better OS [p=0.015] and PFS [p=0.002] for cHPPAC. ConclusionThe combination of HPV-DNA and p16 can be used as an independent prognostic parameter in anal cancer patients.

The influence of human papilloma virus (HPV) infection on the outcome of subjects with anal squamous cell carcinoma.

e15152 Background: HPV infection is a risk factor for the development of anal cancer. P16 expression correlates highly with HPV infection. The influence of HPV infection on the outcome of these subjects has not been well defined. To evaluate the influence of HPV infection on prognosis of subjects with anal squamous cell cancer, a retrospective analysis was conducted. Methods: Subjects with anal squamous cell cancer diagnosed at the University of Arkansas for Medical Sciences between 1992 and 2010, were identified from the tumor registry. The charts were reviewed to confirm the diagnosis, stage, treatment and outcome of the subjects. Paraffin tissue blocks of the subjects were stained for p16 expression using the immunoperoxidase method using mouse monoclonal antibody (Clone E6H4) and CINTek Histology VKit. Slides were scanned to digital file (Aperio CS, Aperio, Vista, CA). Neoplastic regions were analyzed using a color deconvolution algorithm (Aperio). Based on the percentage of pixels with weak, moderate, strong, and negative staining, each slide was given a score between 0-300. Score of 150 and above was designated as positive. P16 positive and negative groups were compared for differences in recurrence-free survival (RFS) and overall survival (OS) via log-rank test. Results: There were 19 deaths observed among 33 study-eligible subjects during 103.2 person-years of follow-up. The median age (quartiles) was 53 (45-61) years. Males were 55%; Caucasians were 94%. All subjects were treated with chemotherapy and radiation. 26 subjects were p16 positive and 7 were p16 negative. The median RFS was 2.99 years for the p16-positive group vs. 1.90 years for the p16-negative group (p = 0.32). The median OS was 3.14 years for p16-positives vs. 2.00 years for p16-negatives, (p = 0.52). Conclusions: 78% of the patients with anal squamous cell cancer in our study were p16-positive. The RFS and OS tended to be longer for patients with p16-positive cancer, but the lack of statistical significance might be explained by the small number of p16-negative subjects. A larger study needs to be conducted to further evaluate the difference. [Table: see text]

The role of inflammation in HPV infection of the Oesophagus

BackgroundSeveral human cancers are known to be associated with inflammation and/or viral infections. However, the influence of tumour-related inflammation on viral uptake is largely unknown. In this study we used oesophageal squamous cell carcinoma (OSCC) as a model system since this type of cancer is associated with chronic irritation, inflammation and viral infections. Although still debated, the most important viral infection seems to be with Human Papillomavirus (HPV). The present study focused on a possible correlation between inflammation, OSCC development and the influence of HPV infection.MethodsA total of 114 OSCC biopsies and corresponding normal tissue were collected at Groote Schuur Hospital and Tygerberg Hospital, Cape Town (South Africa), that were subjected to RNA and DNA isolation. RNA samples were analysed by quantitative Light Cycler RT-PCR for the expression of selected genes involved in inflammation and infection, while conventional PCR was performed on the DNA samples to assess the presence of integrated viral DNA. Further, an in vitro infection assay using HPV pseudovirions was established to study the influence of inflammation on viral infectivity using selected cell lines.ResultsHPV DNA was found in about 9% of OSCC patients, comprising predominantly the oncogenic type HPV18. The inflammatory markers IL6 and IL8 as well as the potential HPV receptor ITGA6 were significantly elevated while IL12A was downregulated in the tumour tissues. However, none of these genes were expressed in a virus-dependent manner. When inflammation was mimicked with various inflammatory stimulants such as benzo-α-pyrene, lipopolysaccharide and peptidoglycan in oesophageal epithelial cell lines in vitro, HPV18 pseudovirion uptake was enhanced only in the benzo-α-pyrene treated cells. Interestingly, HPV pseudovirion infectivity was independent of the presence of the ITGA6 receptor on the surface of the tested cells.ConclusionThis study showed that although the carcinogen benzo-α-pyrene facilitated HPV pseudovirion uptake into cells in culture, HPV infectivity was independent of inflammation and seems to play only a minor role in oesophageal cancer.

Relationship among bacterial vaginosis, local inflammatory response and presence of cervical intraepithelial neoplasia in women with and without human papilloma virus infection

Objective: An assessment of influence of human papilloma virus (HPV) infection on the presence of dysplasia and relationship among the local immune system, HPV infection and bacterial vaginosis (BV). Methods: The study group (n=143) was divided into: experimental arm: positive HPV-DNA sequence with polymerase chain reaction method on the cervix tissue specimen (HPV group, n = 82), control arm: negative HPV-DNA sequence (nHPV group, n=61). Secondarily, the study group was divided into: subgroup with malignant lesions (ML group, n = 95) and subgroup with benign lesions (BL group; n=48). Each patient was evaluated for: bacterial morphotype (Nugent score), cervical inflammation, HPV cervical infection classified by virus subtype, histopathological examinations of the cervix biopsy. Results: In HPV group there was higher prevalence of women who: had their first sexual contact between 16 and 22 years (P < 0.001), had more than 3 previous or actual sexual partners (P < 0.001, P < 0.05; respectively), were unmarried (P < 0.01). We found: significantly higher prevalence of polymorphonuclear cervicitis and Candida albicans ( C. albicans)- hyphae predomination in HPV group, but Gardnerella vaginalis in nHPV group, predomination of benign lesions in nHPV group, prevalence of Trichomonas vaginalis, as well as normal vaginal flora in BL subgroup, but C. albicans - sporae in ML subgroup. The most frequent infections in HPV group were those with HPV type 16 and 53. Conclusion: The local inflammatory response is predominantly expressed by mononuclear infiltration in HPV presence, probably as a result of declined local immunity. In these circumstances, the commensalisms (i.e., C. albicans) flourish.